Point Mutations in RET Proto-Oncogene Exon 10 in Patients with Medullary Thyroid Carcinoma

Background & Aims: Thyroid cancer is the most common endocrine malignancy. Medullary thyroid carcinoma (MTC) is an aggressive malignant tumor arising from parafollicular cells of the thyroid. MTC occurs in hereditary (25%, hMTC) or sporadic (75%, sMTC) forms. The hMTC form has an autosomal dominant inheritance. RET proto-oncogene mutations, especially the 10, 11, and 16 exones, are associated with MTC. The aim of this study was to determine the type and frequency of RET proto-oncogene exon 10 in patients with MTC. Methods: The study participants included 347 individuals, including 207 patients and 140 of their first degree relatives. Genomic DNA was extracted from peripheral leukocytes using salting out/Proteinase K method. All individuals were tested for RET mutations in exon 10 using polymerase chain reaction (PCR)- DNA sequencing method. Results: A total of 14 germline missense RET mutations were identified in cysteine codons 611, 618, and 620 in 11 patients(10 mutation in males, 4 in females), and 3 of their first-degree relatives (frequency: 3.6%) which were as follows: four C611Y (three FMTC, one relative), one C618R (FMTC), one C618S (sMTC), one C620G (sMTC), four C620R (one FMTC, three sMTC), and three C620F (one FMTC, two relatives). The most predominant mutations in exon 10 in our FMTC and sMTC patients were C611Y and C620R, respectively. We did not find any mutations in cysteine codon 609. Conclusion: In the present study, 6 different types of missense mutations were identified in exon 10 of RET in the nonsyndromic form of MTC. Based on the results of this study, mutation detection using DNA sequencing in exons 10, 11, and 16 of RET in patients with MTC and their relatives is recommended.

Point Mutations in RET Proto-Oncogene Exon 10 in Patients with Medullary Thyroid Carcinoma Keywords:

medullary thyroid cancer , RET proto-oncogene , Exon 10 , Germline mutation , Iranian population